C-arm computed tomography compared with positron emission tomography/computed tomography for treatment planning before radioembolization.

The purpose of this study was to determine whether rotational C-arm computed tomography (CT) allows visualization of liver metastases and adds relevant information for radioembolization (RE) treatment planning. Technetium angiography, together with C-arm CT, was performed in 47 patients to determine the feasibility for RE. C-arm CT images were compared with positron emission tomography (PET)/CT images for the detection of liver tumors. The images were also rated according one of the following three categories: (1) images that provide no additional information compared with DSA alone; (2) images that do provide additional information compared with DSA; and (2) images that had an impact on eligibility determination for and planning of the RE procedure. In all patients, 283 FDG-positive liver lesions were detected by PET. In venous contrast-phase CT, 221 (78.1%) and 15 (5.3%) of these lesions were either hypodense or hyperdense, respectively. In C-arm CT, 103 (36.4%) liver lesions were not detectable because they were outside of either the field of view or the contrast-enhanced liver segment. Another 25 (8.8%) and 98 (34.6%) of the liver lesions were either hyperdense or presented primarily as hypodense lesions with a rim enhancement, respectively. With PET/CT as the standard of reference, venous CT and C-arm CT failed to detect 47 (16.6%) and 57 (20.1%) of all liver lesions, respectively. For RE planning, C-arm CT provided no further information, provide some additional information, or had an impact on the procedure in 20 (42.5%), 15 (31.9%) and 12 (25.6%) of patients, respectively. We conclude that C-arm CT may add decisive information in patients scheduled for RE.

Evaluation of endovenous radiofrequency ablation and laser therapy with endoluminal optical coherence tomography in an ex vivo model.

BACKGROUND: This study evaluated the ability of endovascular optical coherence tomography (eOCT) to detect qualitative tissue alteration and quantitative changes of vein wall thickness and vein lumen diameter comparing endovenous radiofrequency ablation (RFA) and endovenous laser therapy (ELT) in an established ex vivo model. METHODS: Endoluminal eOCT was performed by means of a new prototype rotating system (System M1, LightLab Imaging Inc, Boston, Mass) with automatic pullback of 1 mm/s. In the course of an eOCT examination of a 50-mm vein segment, 264 electronic cross section images with a spatial resolution of 15 to 20 mum are acquired. The eOCT scans were performed before and after treatment of each of 13 treated vein segments and of six control vein segments. Thirteen subcutaneous cow foot veins were reperfused in situ, and the defined 50-mm vein segments in the study were treated with RFA (n = 2) and ELT (n = 11). RFA followed the clinical VNUS-Closure protocol (VNUS Medical Technologies, San Jose, Calif) using a 6F 60-mm Closure-Plus catheter. ELT was performed using light of lambda = 980 nm with a laser power of 3 (n = 2), 5 (n = 2), and 7 W (n = 4) with a paced pullback protocol with laser irradiation for 1.5 seconds every 3 mm, resulting in linear endovenous energy densities (LEED) of 15, 25, and 35 J/cm. Using 11 W (n = 3) with a continuous pullback protocol at 3 mm/s resulted in a LEED of 36.5 J/cm. Ten histologic cross sections of each treated and control vein segment were correlated with the corresponding eOCT cross sections to evaluate qualitative representation of vein wall layers and tissue alterations such as ablation and vein wall perforation. In addition, 26 eOCT cross sections of every treated vein segment before and after treatment and every control vein segment were analyzed to calculate quantitative changes in media thickness and vein lumen diameter. RESULTS: In all specimens, qualitative analysis with eOCT demonstrated a clear match with histologic cross sections. A symmetrical, complete, circular disintegration of intima and media structures, without any transmural tissue defects, was shown after RFA. Pronounced semicircular tissue ablations (3 to 14 per 50 mm) and complete vessel wall perforations (0 to 16 per 50 mm) were detected after ELT. The quantitative analysis demonstrated a significant (P < .0001) increase in intima-media thickness after RFA (37.8% to 66.7%) and ELT (11.1% to 45.7%). A significant (P < .0001) reduction of vessel lumen diameter (36.3% to 42.2%) was found after RFA. Owing to the limited number of treated vein segments and inhomogeneous baseline vein lumen diameters, no linear correlation between laser energy level and effects on tissue such as ablation/perforation, media thickening, or vein lumen diameter could be identified. CONCLUSIONS: In our ex vivo cow foot model, eOCT is able to reproduce normal vein wall structures and endovenous acute thermal alterations, such as tissue ablation and vessel wall perforations. Endovenous eOCT images can also be analyzed quantitatively to measure media thickness or vein lumen diameter. Endovascular OCT could become a valuable alternative tool for morphologic investigation of tissue alterations after endovenous thermal procedures.

Endovascular optical coherence tomography ex vivo: venous wall anatomy and tissue alterations after endovenous therapy.

Endovascular optical coherence tomography (OCT) is a new imaging modality providing histology-like information of the venous wall. Radiofrequency ablation (RFA) and laser therapy (ELT) are accepted alternatives to surgery. This study evaluated OCT for qualitative assessment of venous wall anatomy and tissue alterations after RFA and ELT in bovine venous specimens. One hundred and thirty-four venous segments were obtained from ten ex-vivo bovine hind limbs. OCT signal characteristics for different wall layers were assessed in 180/216 (83%) quadrants from 54 normal venous cross-sections. Kappa statistics (kappa) were used to calculate intra- and inter-observer agreement. Qualitative changes after RFA (VNUS-Closure) and ELT (diode laser 980 nm, energy densities 15 Joules (J)/cm, 25 J/cm, 35 J/cm) were described in 80 venous cross-sections. Normal veins were characterized by a three-layered appearance. After RFA, loss of three-layered appearance and wall thickening at OCT corresponded with circular destruction of tissue structures at histology. Wall defects after ELT ranged from non-transmural punctiform damage to complete perforation, depending on the energy density applied. Intra- and inter-observer agreement for reading OCT images was very high (0.90 and 0.88, respectively). OCT allows for reproducible evaluation of normal venous wall and alterations after endovenous therapy. OCT could prove to be valuable for optimizing endovenous therapy in vivo.

Diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of atherosclerotic plaque composition in ex-vivo coronary specimens: a comparison with histology.

BACKGROUND: Both intravascular ultrasound and optical coherence tomography have been purported to accurately detect and characterize coronary atherosclerotic plaque composition. The aim of our study was to directly compare the reproducibility and diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of coronary plaque composition ex vivo as compared with histology. METHODS AND RESULTS: Intravascular ultrasound (20 MHz) and optical coherence tomography imaging was performed in eight heart specimens using motorized pullback. Standard histology using hematoxylin-eosin and van Gieson staining was performed on 4 mum thick slices. Each slice was divided into quadrants and accurately matched cross-sections were analyzed for the presence of fibrous, lipid-rich, and calcified coronary plaque using standard definitions for both intravascular ultrasound and optical coherence tomography and correlated with histology. After exclusion of 145/468 quadrants, we analyzed the remaining 323 quadrants with excellent image quality in each procedure. Optical coherence tomography demonstrated a sensitivity and specificity of 91/88% for normal wall, 64/88% for fibrous plaque, 77/94% for lipid-rich plaque, and 67/97% for calcified plaque as compared with histology. Intravascular ultrasound demonstrated a sensitivity and specificity of 55/79% for normal wall, 63/59% for fibrous plaque, 10/96% for lipid-rich plaque, and 76/98% for calcified plaque. Both intravascular ultrasound and optical coherence tomography demonstrated excellent intraobserver and interobserver agreement (optical coherence tomography: kappa=0.90, kappa=0.82; intravascular ultrasound: kappa=0.87, kappa=0.86). CONCLUSION: Optical coherence tomography is superior to intravascular ultrasound for the detection and characterization of coronary atherosclerotic plaque composition, specifically for the differentiation of noncalcified, lipid-rich, or fibrous plaque.

Influence of xanthohumol on the binding behavior of GABAA receptors and their lateral mobility at hippocampal neurons.

The influence of the xanthohumol from Humulus lupulus L. on the binding of muscimol-Alexa Fluor 532 (Mu-Alexa), a fluorescently labeled GABAA receptor agonist, was studied by fluorescence correlation spectroscopy. An incubation of hippocampal neurons with 75 nM of xanthohumol increased the specific Mu-Alexa binding by approximately 17%, which was selectively found in GABAA receptor Mu-Alexa complexes with hindered lateral mobility [D(bound2) = (0.11 +/- 0.03) microm2/s] as described with midazolam.

Catheter-based intraluminal optical coherence tomography (OCT) of the ureter: ex-vivo correlation with histology in porcine specimens.

Intraluminal optical coherence tomography (OCT) applies coherent light to provide cross-sectional images with a spatial resolution of 10-25 microm. We compared OCT and matching whole-mount histology microscopy sections of porcine upper ureters ex vivo for visualization and delineation of different tissue layers of the ureteral wall. Porcine ureters (six specimens, 24 quadrants) were flushed with normal saline solution prior to insertion of the OCT catheter (diameter, 0.014 inch, OCT wavelength, 1,300+/-20 nm). Cross-sectional OCT images were obtained in marked locations before specimens were fixed in 4% formalin, cut at marked locations, whole-mounted, and stained with hematoxilin and eosin. Visualization and delineation of different tissue layers of the ureteral wall by OCT was compared with matching histology by two independent observers (O1,O2). OCT distinguished tissue layers of the ureteral wall in all quadrants. In OCT images, O1/O2 delineated urothelium and lamina propria in 23/24 quadrants, lamina propria and muscle layer in 19/16 quadrants, inner and outer muscle layer in 13/0 quadrants, and urothelial cell layers in 13/2 quadrants, respectively. Intraluminal OCT provides histology-like images of the ureter in porcine specimens ex vivo and reliably distinguishes between urothelium and deeper tissue layers of the ureteral wall.

Intravascular optical coherence tomography: comparison with histopathology in atherosclerotic peripheral artery specimens.

PURPOSE: Intravascular optical coherence tomography (OCT) is a new imaging modality that provides microstructural information on atherosclerotic plaques and has an axial resolution of 10-20 microm. OCT of coronary arteries characterizes different atherosclerotic plaque components by their distinctive signal patterns. Peripheral human arteries were examined ex vivo by means of OCT, and attempts to distinguish among fibrous, lipid-rich, and calcified atherosclerotic plaques were made based on imaging criteria previously established for coronary arteries. MATERIALS AND METHODS: One hundred fifty-one atherosclerotic arterial segments were obtained from 15 below-knee amputations. OCT imaging criteria for different plaque types (fibrous, lipid-rich, calcified) were established in a subset of 30 arterial segments. The remaining 121 OCT images were analyzed by two independent readers. Each segment was divided into four quadrants. Agreement between histopathology and OCT was quantified by the kappa test of concordance, as were interobserver, intraobserver, and inter-method variability. RESULTS: Four hundred sixty-nine of 484 quadrants (97%) were available for comparison. Sensitivity and specificity for OCT criteria (consensus readers 1 and 2) were 86% and 86% for fibrous plaques, 78% and 93% for lipid-rich plaques, and 84% and 95% for calcified plaques, respectively (overall agreement, 84%). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.84 and 0.87, respectively). The inter-method agreement was 0.74 for consensus OCT versus consensus histology. CONCLUSIONS: OCT of peripheral human arteries ex vivo characterized different atherosclerotic plaque types with a high degree of agreement with histopathologic findings. Findings were comparable to those reported for coronary arteries. OCT promises to improve understanding of the progression or regression of peripheral atherosclerosis in vivo.

HPLC analysis of flavokavins and kavapyrones from Piper methysticum Forst.

A simultaneous HPLC separation of the six major kavapyrones and the flavokavins A-C in an ethanolic extract of Piper methysticum was carried out on a Symmetry C18 column. For quantitative determinations of the flavokavins, calibration curves with correlation coefficients between 0.9986 and 0.9998 were established. Detection limit for each flavokavin of 0.5 ng per injection was measured at 355 nm. The precision of the HPLC analysis was verified by six determinations of the content of flavokavins in the kava extract. Flavokavins A-C contents of 0.62+/-0.01 mg/100 mg, 0.34+/-0.01 mg/100 mg and 0.14+/-0.003 mg/100 mg ethanolic kava extract was found, respectively. From the corresponding relative standard deviation of 1.53, 1.99 and 2.30% the confidential interval (P=95) of the mean value was calculated for each flavokavin. The accuracy of the method was proven by recoveries between 99.2+/-0.3% and 101.1+/-0.4% for the flavokavins A-C.

Critical limb ischemia: hybrid MR angiography compared with DSA.

PURPOSE: To compare a hybrid magnetic resonance (MR) angiography protocol with selective digital subtraction angiography (DSA) in patients with critical limb ischemia. MATERIALS AND METHODS: The study was approved by the institutional review board, and written consent was obtained from all patients. Pretreatment DSA and hybrid MR angiography were performed in 19 consecutive patients (15 men, four women; mean age, 69.8 years; range, 44-86 years). Hybrid MR angiography included submillimeter dual-phase three-dimensional gadolinium-enhanced MR angiography in lower calf and foot, and four-station bolus-chase MR angiography in pelvis, thigh, and upper calf. Three readers identified the target lesion and inflow and outflow segments and determined treatment (bypass graft placement, percutaneous transluminal angioplasty, conservative management, amputation). Results of interobserver and intermethod comparisons were expressed as percentage of agreement and 95% confidence interval (CI). RESULTS: On hybrid MR angiograms, no substantial venous overlay was present and image quality was excellent or adequate in 18 (95%) of 19 limbs. Readers 1, 2, and 3 selected the identical target lesion on the DSA image and the MR angiogram in 18, 17, and 18 of 18 comparable limbs, respectively. Mean percentage of agreement for readers 1 and 3 was 100% (95% CI: 81%, 100%) and for reader 2 was 94% (95% CI: 73%, 100%). Agreement of all three readers was superior with use of MR angiography for determination of inflow segments (13 [72%] of 18 limbs) and outflow segments (17 [94%] of 18 limbs), compared with agreement with use of DSA (13 [68%] of 19 inflow segments, 10 [53%] of 19 outflow segments). Agreement in therapy decisions was higher with DSA (15 [79%] of 19) than with MR angiography (11 [61%] of 18). CONCLUSION: Preliminary data strongly support the combination of submillimeter dual-phase MR angiography in lower calf and foot with four-station bolus-chase MR angiography to extend the utility of MR angiography to patients with critical limb ischemia.

Magnetic resonance angiography in the follow-up of distal lower-extremity bypass surgery: comparison with duplex ultrasound and digital subtraction angiography.

PURPOSE: The danger of limb loss as a consequence of acute occlusion of infrapopliteal bypasses underscores the requirement for careful patient follow-up. The objective of this study was to determine the agreement and accuracy of contrast material-enhanced moving-table magnetic resonance (MR) angiography and duplex ultrasonography (US) in the assessment of failing bypass grafts. In cases of discrepancy, digital subtraction angiography (DSA) served as the reference standard. MATERIALS AND METHODS: MR angiography was performed in 24 consecutive patients with 26 femorotibial or femoropedal bypass grafts. Each revascularized limb was divided into five segments--(i) native arteries proximal to the graft; (ii) proximal anastomosis; (iii) graft course; (iv) distal anastomosis; and (v) native arteries distal to the graft-resulting in 130 vascular segments. Three readers evaluated all MR angiograms for image quality and the presence of failing grafts. The degree of stenosis was compared to the findings of duplex US, and in case of discrepancy, to DSA findings. Two separate analyses were performed with use of DSA only and a combined diagnostic endpoint as the reference standard. RESULTS: Image quality was rated excellent or intermediate in 119 of 130 vascular segments (92%). Venous overlay was encountered in 26 of 130 segments (20%). In only two segments was evaluation of the outflow region not feasible. One hundred seventeen of 130 vascular segments were available for quantitative analysis. In 109 of 117 segments (93%), MR angiography and duplex US showed concordant findings. In the eight discordant segments in seven patients, duplex US overlooked four high-grade stenoses that were correctly identified by MR angiography and confirmed by DSA. Percutaneous transluminal angioplasty was performed in these cases. In no case did MR angiography miss an area of stenosis of sufficient severity to require treatment. Total accuracy for duplex US ranged from 0.90 to 0.97 depending on the reference standard used, whereas MR angiography was completely accurate (1.00) regardless of the standard definition. CONCLUSION: Our data strongly suggest that the accuracy of MR angiography for identifying failing grafts in the infrapopliteal circulation is equal to that of duplex US and superior to that of duplex US in cases of complex revascularization. MR angiography should be included in routine follow-up of patients undergoing infrapopliteal bypass surgery.

Primary endovascular stent placement for focal infrarenal aortic stenosis: initial and midterm results.

The objectives of this retrospective study were to determine the technical success, safety, and midterm results of primary stent placement of infrarenal aortic stenosis. Eight stenoses and one occlusion were treated with stent placement after balloon pre-dilation. Primary technical success was achieved in all patients. Five patients showed reperfusion or restored normal direction of flow of the inferior mesenteric artery. No complications occurred. There was a mean follow-up of 12 months (range, 3-20 months). Primary clinical and hemodynamic patency rates were 100% on follow-up examinations. Stent placement after balloon pre-dilation in properly selected patients with isolated infrarenal aortic stenosis is a promising durable treatment.

Positive cooperation of protoberberine type 2 alkaloids from Corydalis cava on the GABA(A) binding site.

Protoberberine alkaloids from the rhizomes of Corydalis cava were investigated with regard to their influence on the GABA A receptor using radioreceptor assays. Whereas the protoberberine type 2 alkaloids, isoapocavidine, corydaline, tetrahydropalmatine, scoulerine and isocorypalmine, increased the specific [(3)H]BMC-binding in a range of 21 - 49 %, the protoberberine type 1 alkaloids, palmatine, coptisine, dehydroapocavidine, and dehydrocorydaline, had no influence on the binding behaviour of the GABA A receptor. To confirm the modulatory activity of the protoberberine type 2 alkaloids on living cells, GABA A receptor binding studies were performed by fluorescence correlation spectroscopy (FCS) using hippocampal neurons and the fluorescently labelled ligand, muscimol-Alexa (Mu-Alexa). The incubation of hippocampal neurons with 7.5 nM Mu-Alexa showed a specific binding of 5.25 nM (70 %). The evaluation of the autocorrelation curve revealed two different mobilities of receptor ligand complexes, D bound1 = (2.8 +/- 0.91) microm 2/s for the free lateral mobility and D bound2 = (0.14 +/- 0.05) microm 2/s for the hindered mobility. An incubation of hippocampal neurons with 7.5 nM Mu-Alexa and 7.5 nM scoulerine showed a maximal increase of the specific Mu-Alexa binding of approximately 27 % by selectively modulating the amount of receptor-ligand complexes with a hindered mobility (9 % to 27 %).

Lateral mobility and specific binding to GABA(A) receptors on hippocampal neurons monitored by fluorescence correlation spectroscopy.

The binding behavior of a fluorescently labeled muscimol derivative to the GABA(A) receptor was analyzed at rat hippocampal neurons by fluorescence correlation spectroscopy. After muscimol had been labeled with the fluorophore Alexa Fluor 532, specific binding constants for binding of the dye-labeled ligand (Mu-Alexa) to the GABA(A) receptor were determined. We found a high specific binding affinity of Mu-Alexa with a K(D) value of 3.4 +/- 0.5 nM and a rate constant of ligand-receptor dissociation (k(diss)) of (5.37 +/- 0.95) x 10(-2) s(-1). A rate constant of ligand-receptor association (k(ass)) of (1.57 +/- 0.28) x 10(7) L mol(-1) s(-1) was calculated. The following diffusion coefficients were observed: D(free) = 233 +/- 20 microm(2)/s (n = 66) for free diffusing Mu-Alexa, D(bound1) = 2.8 +/- 0.9 microm(2)/s (n = 64) for the lateral mobility, and D(bound2) = 0.14 +/- 0.05 microm(2)/s (n = 56) for the hindered mobility of the GABA(A) receptor-ligand complex in the cell membrane. Saturation of Mu-Alexa binding was observed at a concentration of 50 nM. A maximum number of binding sites [B(max) = 18.4 +/- -0.4 nM (n = 5)] was found. Similar K(i) values of 4.5 +/- 1.0 nM for nonlabeled muscimol and 8.8 +/- 1.8 nM for Mu-Alexa were found by RRAs using [(3)H]muscimol as a radioligand. A concentration-dependent increase in the level of specific Mu-Alexa binding was demonstrated by the positive cooperative activity of co-incubated midazolam, which was selectively found in GABA(A) receptor-ligand complexes with hindered mobility.

High-resolution MR imaging of human atherosclerotic femoral arteries in vivo: validation with intravascular ultrasound.

PURPOSE: To establish a magnetic resonance (MR) imaging protocol for noninvasive in-vivo analysis of atherosclerotic femoral artery segments in humans and to compare the results to those of intravascular ultrasonography (IVUS). MATERIALS AND METHODS: In seven patients with peripheral arterial occlusive disease, 20 femoral arterial segments per person were examined by high-resolution (HR) MR imaging and IVUS. Comparison was possible in 123 of 140 segments. MR imaging was performed at 1.5 T with use of a three-dimensional (3D) time-of-flight sequence with an in-plane resolution of 0.78 x 0.49 mm(2). 3D contrast-enhanced MR angiography was used for exact positioning of the HR MR imaging slices. IVUS (3.5 F, 40 MHz) was performed with use of a motorized pullback system. Parameters analyzed included cross-sectional lumen area (LA), vessel area (VA), and extent of vessel wall calcification. RESULTS: Agreement between IVUS and HR MR imaging was analyzed with use of the Bland-Altman method. The paired LA measurements were in close agreement: the Bland-Altman mean bias in LA was -0.4 mm with a precision of +/-5.1 mm (P =.062). As a result of dorsal echo extinction in IVUS, VA measurements were feasible in only 74 of 140 segments. VA measurements were moderately correlated (r = 0.74; P <.0001), and a 25% overestimation by HR MR imaging compared to IVUS was observed. Intra- and interobserver comparisons for LA and VA measured with HR MR imaging did not show significant differences. Vessel wall calcifications were classified with a sensitivity of 91%, a specificity of 93%, and an accuracy of 93%. CONCLUSIONS: The MR imaging protocol introduced in the present study permits precise assessment of LA and extent of calcification in peripheral arterial occlusive disease in vivo. HR MR imaging shows high concordance with IVUS and may have the potential for noninvasive therapy monitoring.

MR imaging of the brain in pediatric patients: diagnostic value of HASTE sequences.

OBJECTIVE: The objective of this study was to determine the diagnostic value of half-Fourier single-shot turbo spin-echo (HASTE) sequences in MR imaging of the brain in pediatric patients. SUBJECTS AND METHODS: HASTE sequences were performed in 80 infants and children. Two radiologists who were unaware of the patients' medical histories independently reviewed the images for the presence of nine findings: defects of the parenchyma, hypoplasia or agenesis of the corpus callosum, edema, signs of increased intracranial pressure, myelination disorders, migration disorders, malformations, tumors, and widening of spaces of the cerebrospinal fluid. A conventional MR imaging examination that served as the reference examination was evaluated by the same two radiologists in a final consensus interpretation. The findings detected on the HASTE images were compared with the findings seen on the conventional MR images. The sensitivity and specificity of HASTE sequences were calculated, and Cohen's kappa statistic was used to determine interobserver agreement. RESULTS: Both radiologists correctly diagnosed all 20 defects of the parenchyma that were present in the patients. Radiologist 1 correctly identified 20 and radiologist 2 correctly identified 21 of the 22 patients with hypoplasia or agenesis of the corpus callosum. Both radiologists correctly diagnosed edema in eight of the nine patients in whom edema was present, and both correctly identified signs of increased intracranial pressure in eight of the nine children who had this condition. Radiologist 1 correctly diagnosed seven and radiologist 2 correctly identified nine of the 11 cases of myelination disorders. Both radiologists correctly diagnosed six of the 14 cases with migration disorders. All 13 brain malformations present in the patients were correctly identified by both reviewers. Both radiologists correctly identified all 11 patients with tumors, and both correctly identified all 35 patients with widening of spaces of the cerebrospinal fluid. CONCLUSION: HASTE images are highly sensitive for excluding the presence of brain tumor, hydrocephalus, or malformations of the brain. HASTE images are not reliable for evaluating patients with suspected myelination disorders or migration disorders.